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绝经后妇女胰腺癌的前瞻性靶向血清代谢组学研究。

A Prospective Targeted Serum Metabolomics Study of Pancreatic Cancer in Postmenopausal Women.

机构信息

Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, Texas.

Center for Innovations in Quality, Effectiveness and Safety (IQuESt), Michael E. DeBakey VA Medical Center, Houston, Texas.

出版信息

Cancer Prev Res (Phila). 2019 Apr;12(4):237-246. doi: 10.1158/1940-6207.CAPR-18-0201. Epub 2019 Feb 5.

Abstract

To examine the association between metabolic deregulation and pancreatic cancer, we conducted a two-stage case-control targeted metabolomics study using prediagnostic sera collected one year before diagnosis in the Women's Health Initiative study. We used the LC/MS to quantitate 470 metabolites in 30 matched case/control pairs. From 180 detectable metabolites, we selected 14 metabolites to be validated in additional 18 matched case/control pairs. We used the paired test to compare the concentrations of each metabolite between cases and controls and used the log fold change (FC) to indicate the magnitude of difference. FDR adjusted q-value < 0.25 was indicated statistically significant. Logistic regression model and ROC curve analysis were used to evaluate the clinical utility of the metabolites. Among 30 case/control pairs, 1-methyl-l-tryptophan (L-1MT) was significantly lower in the cases than in the controls (log FC = -0.35; q-value = 0.03). The area under the ROC curve was 0.83 in the discrimination analysis based on the levels of L-1MT, acadesine, and aspartic acid. None of the metabolites was validated in additional independent 18 case/control pairs. No significant association was found between the examined metabolites and undiagnosed pancreatic cancer.

摘要

为了研究代谢失调与胰腺癌之间的关系,我们在妇女健康倡议研究中进行了一项两阶段病例对照靶向代谢组学研究,使用的是诊断前一年采集的血清。我们使用 LC/MS 定量分析了 30 对匹配的病例/对照中的 470 种代谢物。在 180 种可检测到的代谢物中,我们选择了 14 种代谢物在另外 18 对匹配的病例/对照中进行验证。我们使用配对 t 检验比较病例和对照之间每种代谢物的浓度,并使用对数倍数变化(FC)表示差异的大小。FDR 调整的 q 值<0.25 表示具有统计学意义。逻辑回归模型和 ROC 曲线分析用于评估代谢物的临床实用性。在 30 对病例/对照中,1-甲基-l-色氨酸(L-1MT)在病例中的浓度明显低于对照(log FC = -0.35;q 值 = 0.03)。基于 L-1MT、腺苷酸和天冬氨酸水平的判别分析中,ROC 曲线下面积为 0.83。在另外 18 对独立的病例/对照中,没有验证到其他代谢物。所检查的代谢物与未诊断的胰腺癌之间没有发现显著关联。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d27/6445762/8fe0bd6b6c71/nihms-1520874-f0001.jpg

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